IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2 + Vγ6 + γδT cells

Aoi Akitsu, Harumichi Ishigame, Shigeru Kakuta, Soo Hyun Chung, Satoshi Ikeda, Kenji Shimizu, Sachiko Kubo, Yang Liu, Masayuki Umemura, Goro Matsuzaki, Yasunobu Yoshikai, Shinobu Saijo, Yoichiro Iwakura

    Research output: Contribution to journalArticle

    51 Citations (Scopus)

    Abstract

    Interleukin-17 (IL-17)-producing γδT (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4 + and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4 + T cells direct γδT-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6 + subset of CCR2 + γδT cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδT cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6 + cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.

    Original languageEnglish
    Article number7464
    JournalNature communications
    Volume6
    DOIs
    Publication statusPublished - Jun 25 2015

      Fingerprint

    All Science Journal Classification (ASJC) codes

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

    Cite this